Guselkumab-Treated Patients with Plaque Psoriasis Who Achieved Complete Skin Clearance for ≥ 156 Consecutive Weeks: A Post-Hoc Analysis From the VOYAGE 1 Clinical Trial.

BACKGROUND: Treatment of moderate-to-severe plaque psoriasis with biologics, such as guselkumab, has demonstrated greater efficacy over traditional non-biologic treatments. However, given patient diversity, greater understanding of the relationship between patient characteristics, positive clinical outcomes, and long-term response to biologics is crucial for optimizing treatment choices. MATERIALS AND METHODS: This post-hoc analysis of the 5-year VOYAGE 1 clinical trial compares baseline characteristics of patients maintaining a Psoriasis Area and Severity Index (PASI) score of 0 at all visits for ≥ 156 consecutive weeks (PASI = 0 group) with those that never achieve PASI = 0 (comparator group), using descriptive statistics and a multiple logistic regression model. Guselkumab plasma trough concentrations in both response groups were assessed from Weeks 4-156. RESULTS: Of patients who started guselkumab treatment at Week 0 or at Week 16 after switching from placebo, 22.7% (112/494) maintained PASI = 0 for ≥ 156 consecutive weeks. Numerical differences in baseline characteristics, including age, obesity, diabetes, PASI score, disease duration, smoking status, and psoriatic arthritis comorbidity, were identified between the PASI = 0 group and comparator group. Plasma guselkumab levels were consistently higher in the PASI = 0 group. Multiple logistic regression analysis revealed absence of diabetes, lower Dermatology Life Quality Index score at baseline, and higher Week 4 guselkumab plasma concentration as significantly (p < 0.05) associated with the PASI = 0 group. CONCLUSION: A substantial (22.7%) number of guselkumab-treated patients in the VOYAGE 1 clinical trial maintained complete skin clearance for a consecutive period of ≥ 156 weeks. Factors associated with this outcome may suggest clinical benefits of holistic treatment approaches. TRIAL REGISTRATION: NCT02207231.

Long-term management of pediatric psoriasis with ixekizumab: a case report.

Psoriasis in pediatric patients is uncommon and the management of moderate-to-severe cases can be challenging. We report the case of a 17-year-old girl who presented with severe plaque psoriasis unresponsive to UVB phototherapy. The Psoriasis Area Severity Index (PASI) was 18 and the Dermatology Life Quality Index was 24. We decided to prescribe ixekizumab, observing complete skin clearance after only 8 weeks. The patient is still on treatment with no reported adverse events after two years.

Secukinumab demonstrates superiority over narrow-band ultraviolet B phototherapy in new-onset moderate to severe plaque psoriasis patients: Week 52 results from the STEPIn study.

BACKGROUND: Biologic treatments have been studied mainly in patients with a long-term history of psoriasis and previous treatment failures. OBJECTIVES: The purpose of this primary analysis of the STEPIn study is to determine whether early intervention with secukinumab in patients with new-onset moderate to severe plaque psoriasis is superior to standard of care treatment with narrow band ultraviolet B (nb-UVB) phototherapy. METHODS: The STEPIn study is a randomized, open-label, multicentre study to investigate early intervention with 52 weeks of secukinumab 300 mg administered subcutaneously versus standard treatment with nb-UVB phototherapy in patients with new-onset (≤12 months) moderate to severe plaque psoriasis (NCT03020199). The primary and additional secondary endpoints were ≥90% improvement in Psoriasis Area and Severity Index (PASI 90) at Week 52 and Investigator's Global Assessment (IGA mod 2011) 0/1 response at Week 52, respectively. RESULTS: In the secukinumab and nb-UVB study arms, 77/80 and 76/80 randomized patients received at least one dose of study treatment, respectively. The primary endpoint was achieved: 91.1% (70/77) of patients achieved a PASI 90 response at Week 52 in the secukinumab arm versus 42.3% (32/76) in the nb-UVB arm (p < 0.0001, odds ratio [OR] estimate [95% confidence intervals, CI] = 16.3 [5.6, 46.9]). The additional secondary endpoint was also achieved: 85.7% of patients achieved an IGA 0/1 response at Week 52 in the secukinumab arm versus 36.8% in the nb-UVB arm (p < 0.0001). The safety data were consistent with the safety profiles of secukinumab and nb-UVB with no new or unexpected safety signals. CONCLUSIONS: Secukinumab was superior to nb-UVB in treating patients with new-onset moderate to severe plaque psoriasis. The high and sustained skin clearance observed indicates that biologic treatment for psoriasis may be more effective if used early in the disease course.

A real-world economic analysis of biologic therapies for moderate-to-severe plaque psoriasis in Italy: results of the CANOVA observational longitudinal study.

BACKGROUND: Psoriasis is a chronic immune-mediated inflammatory skin disease which can also involve joints. It is often associated with burdensome comorbidities which negatively impact prognosis and quality of life (QoL). Biologic agents have been shown to be effective in controlling disease progression, but their use is associated with higher costs compared with traditional systemic treatments. The economic analysis of the CANOVA (EffeCtiveness of biologic treAtmeNts for plaque psOriasis in Italy: an obserVAtional longitudinal study of real-life clinical practice) study aims to assess the costs and cost-effectiveness of biologics in a real-world context in Italy. METHODS: The annualised overall direct costs of moderate-to-severe plaque psoriasis management, the annualised cost of biologic drugs and the cost per responder in the Italian National Health System perspective were assessed. More specifically, the cost per response and cost per sustained response of the most prescribed biologic therapies for the treatment of moderate-to-severe plaque psoriasis within the CANOVA study were assessed using the Psoriasis Area Severity Index (PASI) at several score levels (75, 90 and 100%). RESULTS: The most frequently used biologic therapies for plaque psoriasis were secukinumab, ustekinumab, adalimumab originator, and ixekizumab. Cost of biologics was the driver of expenditure, accounting for about 98% of total costs. Adalimumab originator was the biologic with the lowest cost per responder ratio (range: €7848 - €31,378), followed by secukinumab (range: €9015 - €33,419). Ustekinumab (range: €11,689 - €39,280) and ixekizumab (range: €11,092 - €34,289) ranked respectively third and fourth, in terms of cost-effectiveness ratio. As concerns the cost per sustained response analysis, secukinumab showed the lowest value observed (€21,375) over the other options, because of its high response rate (86% vs. 60-80%), which was achieved early in time. CONCLUSION: Biologic therapy is a valuable asset for the treatment of moderate-to-severe plaque psoriasis. Concomitant assessment of treatment costs against the expected therapeutic response over time can provide physicians and payers additional insights which can complement the traditional risk-benefit profile assessment and drive treatment decisions.

A Comprehensive Patient and Public Involvement Program Evaluating Perception of Cannabis-Derived Medicinal Products in the Treatment of Acute Postoperative Pain, Nausea, and Vomiting Using a Qualitative Thematic Framework.

Introduction: Cannabis-derived medicinal products (CDMPs) have antiemetic properties and in combination with opioids have synergistic analgesic effects in part signaling through the delta and kappa opioid receptors. The objective of this patient and public involvement program was to determine perception of perioperative CDMPs in our local population to inform design of a clinical trial. Methods: A qualitative evaluation was conducted utilizing a focus group, semistructured interviews and a community event. Analysis was conducted through the framework methodology. Verbatim transcriptions were coded categorically into analytical frameworks for thematic analysis. Emergent themes and associated degree of consensus/dissent were determined. The participant cohort was composed of a group of patients and relatives representative of the target population (M:F=1:1, age range 33-85). Results: Most common coding categories in thematic analysis framework included side-effect profile, trial schedule of events, and safety. Consensus was that potential benefits of CDMPs were attractive compared with the known risk profile of opioid use. Decrease in opioid dependence was agreed to be an appropriate clinical end-point for a randomized controlled clinical trial and there was concurrence of positive opinion of a therapeutic schedule of 5 days. Negative CDMP perceptions included addiction, dysphoria, and adverse effects in psychiatric subpopulations. Sublingual or oral administration was the most acceptable route of administration, with some expressing that inhalation delegitimizes therapeutic properties. Conclusions: The perception of postoperative CDMP therapy was overwhelmingly positive in this West London population. The data from this thematic analysis will inform protocol development of clinical trials to determine analgesic and antiemetic efficacy of CDMPs.

Treatment of psoriasis and psoriatic arthritis.

Skin and joint manifestations associated with psoriasis and psoriatic arthritis (PsA) can significantly impact a patient's quality of life. Successful treatment is imperative in order to improve signs and symptoms of the disease, and to alleviate physical or psychological distress. For patients with mild psoriasis with or without PsA, topical agents and targeted phototherapy are appropriate treatments for psoriasis. Systemic therapies, such as methotrexate and phototherapy are recommended options for patients with more severe psoriasis, but their long-term use is hindered by safety concerns. Advancements in understanding the pathogenesis of psoriasis, including the role of T cells and cytokines, have been crucial to the development of biological therapies. These target the immune system and are suitable options for patients with extensive disease. Biological therapies for the treatment of psoriasis include targeted therapies (alefacept) and anti-cytokine therapies (anti-tumour necrosis factor [TNF] therapies [adalimumab, etanercept, infliximab] and a monoclonal antibody against interleukin [IL]-12 and IL-23 [ustekinumab]). Patients with PsA should be treated appropriately in order to improve symptoms and inhibit structural joint damage. Non-steroidal anti-inflammatory drugs or local intra-articular injections of corticosteroids can be used successfully in patients with mild PsA; however, neither treatment prevents the development of structural joint damage. For patients with moderate to severely active PsA, disease-modifying antirheumatic drugs (such as methotrexate), TNF inhibitor treatments (adalimumab, etanercept, infliximab and golimumab) or their combination are considered first-line treatment. This review provides a brief overview of treatment options for psoriasis and PsA, with an emphasis on the efficacy and safety of anti-TNF therapies.

Long-term ustekinumab treatment for refractory type I pityriasis rubra pilaris.

BACKGROUND: Pityriasis rubra pilaris is a rare, chronic erythematous squamous disorder of unknown etiology. The disease is characterized initially by small follicular papules that coalesce into yellowish pink scaly plaques, palmoplantar keratoderma, diffuse furfuraceous scale of the scalp, and frequent progression to exfoliative erythroderma. Generally it is difficult to discern pityriasis rubra pilaris from other skin conditions but key-clinical features help in the diagnosis such as "islands" of spared skin within generalized erythroderma, follicular keratotic plugs, and an orange hue of the involved skin. Treatment options include topical vitamin D analogues, keratolytics, systemic acitretin, methotrexate, cyclosporine, azathioprine, fumaric acid esters, phototherapy, and anti-TNFα agents. Cases, of pityriasis rubra pilaris, successfully treated with a short-course ustekinumab therapy, have been reported. MAIN OBSERVATIONS: We report a 31-year-old man with pityriasis rubra pilaris, refractory to conventional treatments, successfully treated with ustekinumab monotherapy for over 64 weeks. After failing conventional systemic agents (cyclosporine, aciretin and methotrexate), ustekinumab 45 mg has been prescribed, with the same dosing regimen as in psoriasis. The patient improved dramatically within 4 weeks of the first injection, with markedly less erythema and pruritus. Long-term control of the disease of the disease was achieved (64 weeks of treatment). CONCLUSION: We report this case in order to show the striking and rapid efficacy of ustekinumab in reducing the signs and symptoms of the disease. Complete remission was achieved after the third injection, but also a long-term control of the disease. The therapy was well-tolerated in our patient and no adverse events occurred.

Efficacy and safety of etanercept in psoriasis after switching from other treatments: an observational study.

Since targeted biologic treatments have been introduced for the treatment of plaque-type psoriasis and psoriatic arthritis, switching between different medications has become necessary in selected patients, particularly after treatment failures. To evaluate the efficacy and safety of etanercept treatment in adult patients with psoriasis after failure to respond to other previous therapies. In particular, the differences in efficacy profiles after switching from traditional (cyclosporine [ciclosporin], methotrexate, retinoids, fumaric acid esters, psoralen plus UVA therapy, corticosteroids) or biologic (infliximab, efalizumab) treatments were analyzed. The study included 124 patients affected by plaque-type psoriasis who received etanercept administered subcutaneously at a dosage of 50 mg twice weekly for 12 weeks, followed by 25 mg twice weekly for an additional 12 weeks, and 110 patients affected by psoriatic arthritis who were treated with etanercept 25 mg twice weekly in a continuous regimen, after a 12-week period of treatment with etanercept 50 mg twice weekly. Efficacy results were consistent in both groups of patients (plaque-type psoriasis and psoriatic arthritis), as expressed by the percentage of patients who achieved Psoriasis Area and Severity Index (PASI) 50 and PASI 75 scores. Among psoriatic arthritis patients, the mean pain Visual Analog Scale (VAS) score showed a substantial reduction during the treatment course, from 67.2 at week 0 to 15.8 at week 24. After 24 weeks, among patients with plaque-type psoriasis who had not previously received biologic therapies, 89.9% of patients achieved PASI 50 and 75.3% achieved PASI 75, while among patients who had received biologic therapies, 69.6% of patients achieved PASI 50 and 65.2% achieved PASI 75. In addition, 92.3% of patients with psoriatic arthritis who had not previously received biologic therapies achieved PASI 50 and 73.8% achieved PASI 75, while among patients who had received biologic therapies, 45.8% of patients achieved PASI 50 and 29.2% achieved PASI 75. Our study demonstrated that etanercept was more effective in those patients who had not previously received other biologic therapies than in those who had. The results of the present study indicate that etanercept may represent a valid, effective, and well tolerated therapeutic alternative even after failure to respond to traditional and other biologic therapies.

Different applications of monochromatic excimer light in skin diseases.

BACKGROUND: Ultraviolet radiation has been used for curative purposes in dermatologic conditions, especially in the last 30 years. OBJECTIVES: We analyzed the efficacy of monochromatic excimer light in psoriasis, palmoplantar pustulosis, vitiligo, mycosis fungoides and alopecia areata, and to examine potential new indications. METHODS: Two hundred seventy-nine patients with common and persistent skin diseases were enrolled in an open prospective study: 152 patients with stable and localized plaque psoriasis, 47 with palmoplantar psoriasis, 7 with palmoplantar pustulosis, 32 with vitiligo, 11 with prurigo nodularis, 9 with mycosis fungoides stage Ia, 8 with alopecia, 5 with localized scleroderma, 5 with genital lichen sclerosus, and 3 with granuloma annulare. The 308 nm excimer light was used at a power density of 48 mW/cm(2). An average of 12 sessions (range, 6-18), one session per week, was performed and yielded a total dose range of 4-12.5 J/cm(2). Clinical response was assessed using photos, biopsies, and specific clinical scores. Patients were monitorized for 6 and 12 months for psoriasis, 12 months for mycosis fungoides, and 4 months for the remaining conditions. RESULTS: We observed complete remission in more than 50% of patients with plaque psoriasis and palmoplantar dermatoses, respectively, complete remission in all patients affected by mycosis fungoides, excellent repigmentation in one third of vitiligo patients, hair regrowth in three patients with alopecia areata, an overall improvement in prurigo nodularis, a partial remission in patients affected by localized scleroderma, and a complete remission in most of the patients with genital lichen sclerosus and granuloma annulare. CONCLUSIONS: Our study confirms the use of monochromatic excimer light as a valid choice for the treatment of psoriasis, vitiligo, and mycosis fungoides; we also observed and report for the first time that monochromatic excimer light produces a therapeutic response in prurigo nodularis, localized scleroderma, genital lichen sclerosus, and granuloma annulare.

Ascorbate up-regulates MLH1 (Mut L homologue-1) and p73: implications for the cellular response to DNA damage.

We have found previously that ascorbic acid (vitamin C), as well as acting as a radical scavenger, may modulate the expression of several genes [i.e. fra-1, glutathione S-transferase Pi (GSTpi) and Mut L homologue-1 (MLH1)] in human keratinocytes. In the present paper, we demonstrate that MLH1, as well as its downstream target p73, can be positively modulated by this antioxidant vitamin, indeed, up-regulation of the two mRNAs was observed after just 2 h, and increased further up to 16 h of treatment. Modulation of MLH1 and p73 gene expression improves cellular susceptibility to apoptosis triggered by the DNA-damaging agent cisplatin. Indeed, in ascorbate-supplemented cells, increased cisplatin-induced apoptosis was seen, involving activation of the MLH1/c-Abl/p73 signalling cascade. Our results were further confirmed by studies performed on genetically defined mutants, i.e. mouse embryo fibroblasts derived from knock-out animals for c-Abl or p53, as well as human colon carcinoma cell lines deficient in MLH1. The increased sensitivity to cisplatin observed in ascorbate-loaded cells appeared to be dependent exclusively on MLH1 and c-Abl expression, and independent of p53. These data suggest a potential mechanism accounting for the anti-carcinogenic and anti-cancer activities of vitamin C.